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BACKGROUND: Globally, the rate of antiretroviral therapy coverage for pregnant women living with human immunodeficiency virus (HIV) increased by 38% between 2010 and 2015 but only by 2% between 2016 and 2020. OBJECTIVES: We aimed to determine the prevalence of vertical transmission of HIV among infants from mothers living with HIV and associated factors in the Eastern Lake Zone and Southern Highland of Tanzania from January to December 2022. METHODS: This retrospective cross-sectional study extracted data from the Open Laboratory Data Repository database collected from January to December 2022 at 93 health facilities. A total of 1,411 infants exposed to HIV from the Mbeya (851), Songwe (304), and Mara regions (256) were enrolled. RESULTS: The prevalence for vertical transmission of HIV was 2.48% (35/1411). We observed a non-significant difference in the prevalence of vertical transmission in children whose first test was done below six weeks of life (1.89%) and other age groups (2.52-2.62%) (p < 0.917). Children not given antiretroviral prophylaxis had eleven times higher odds of acquiring infection (AOR 11.39, 95% CI: 3.61-35.97). Mothers who were not on ART during pregnancy had three times the odds of transmitting HIV to their infants (AOR 3.03, 95%CI: 0.91-10.15). CONCLUSIONS: We found a low prevalence of vertical transmission of HIV compared to previous studies done in Tanzania. The use of ART prophylaxis for infants exposed to HIV is significantly associated with the low rate of HIV transmission.
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Infecciones por VIH , Transmisión Vertical de Enfermedad Infecciosa , Complicaciones Infecciosas del Embarazo , Humanos , Transmisión Vertical de Enfermedad Infecciosa/estadística & datos numéricos , Tanzanía/epidemiología , Infecciones por VIH/transmisión , Infecciones por VIH/epidemiología , Infecciones por VIH/tratamiento farmacológico , Estudios Transversales , Femenino , Prevalencia , Estudios Retrospectivos , Lactante , Adulto , Embarazo , Masculino , Recién Nacido , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/virología , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Adulto Joven , Factores de RiesgoRESUMEN
Particulate organic nitrate (pON) can be a major part of secondary organic aerosol (SOA) and is commonly quantified by indirect means from aerosol mass spectrometer (AMS) data. However, pON quantification remains challenging. Here, we set out to quantify and characterize pON in the boreal forest, through direct field observations at Station for Measuring Ecosystem Atmosphere Relationships (SMEAR) II in Hyytiälä, Finland, and targeted single-precursor laboratory studies. We utilized a long time-of-flight AMS (LToF-AMS) for aerosol chemical characterization, with a particular focus to identify C x H y O z N+ ("CHON+") fragments. We estimate that during springtime at SMEAR II, pON (including both the organic and nitrate part) accounts for â¼10% of the particle mass concentration (calculated by the NO+/NO2 + method) and originates mainly from the NO3 radical oxidation of biogenic volatile organic compounds. The majority of the background nitrate aerosol measured is organic. The CHON+ fragment analysis was largely unsuccessful at SMEAR II, mainly due to low concentrations of the few detected fragments. However, our findings may be useful at other sites as we identified 80 unique CHON+ fragments from the laboratory measurements of SOA formed from NO3 radical oxidation of three pON precursors (ß-pinene, limonene, and guaiacol). Finally, we noted a significant effect on ion identification during the LToF-AMS high-resolution data processing, resulting in too many ions being fit, depending on whether tungsten ions (W+) were used in the peak width determination. Although this phenomenon may be instrument-specific, we encourage all (LTOF-) AMS users to investigate this effect on their instrument to reduce the possibility of incorrect identifications.
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Global efforts to deliver internationally agreed goals to reduce carbon emissions, halt biodiversity loss, and retain essential ecosystem services have been poorly integrated. These goals rely in part on preserving natural (e.g., native, largely unmodified) and seminatural (e.g., low intensity or sustainable human use) forests, woodlands, and grasslands. To show how to unify these goals, we empirically derived spatially explicit, quantitative, area-based targets for the retention of natural and seminatural (e.g., native) terrestrial vegetation worldwide. We used a 250-m-resolution map of natural and seminatural vegetation cover and, from this, selected areas identified under different international agreements as being important for achieving global biodiversity, carbon, soil, and water targets. At least 67 million km2 of Earth's terrestrial vegetation (â¼79% of the area of vegetation remaining) required retention to contribute to biodiversity, climate, soil, and freshwater conservation objectives under 4 United Nations' resolutions. This equates to retaining natural and seminatural vegetation across at least 50% of the total terrestrial (excluding Antarctica) surface of Earth. Retention efforts could contribute to multiple goals simultaneously, especially where natural and seminatural vegetation can be managed to achieve cobenefits for biodiversity, carbon storage, and ecosystem service provision. Such management can and should co-occur and be driven by people who live in and rely on places where natural and sustainably managed vegetation remains in situ and must be complemented by restoration and appropriate management of more human-modified environments if global goals are to be realized.
Retención de la vegetación natural para salvaguardar la biodiversidad y la humanidad Resumen Hoy en día hay muy poca integración de los esfuerzos mundiales para alcanzar los objetivos internacionales de reducción de las emisiones de carbono, impedimento de la pérdida de biodiversidad y conservación de los servicios ambientales esenciales. Estos objetivos dependen parcialmente de la conservación de los bosques, selvas y praderas naturales (por ejemplo, nativos y en su mayoría sin alteraciones) y seminaturales (por ejemplo, de uso humano sostenible o de baja intensidad). Obtuvimos de manera empírica objetivos espacialmente explícitos, cuantitativos y basados en áreas para la conservación de la vegetación terrestre natural y seminatural (por ejemplo, nativa) en todo el mundo para mostrar cómo unificar los objetivos internacionales. Usamos un mapa de 250 m de resolución de la cubierta vegetal natural y seminatural y, a partir de él, seleccionamos las áreas identificadas como importantes en diferentes acuerdos internacionales para alcanzar los objetivos globales de biodiversidad, carbono, suelo y agua. Al menos 67 millones de km2 de la vegetación terrestre de la Tierra (â¼79% de la superficie de vegetación restante) requieren ser conservados para contribuir a los objetivos de conservación de la biodiversidad, el clima, el suelo y el agua dulce en virtud de cuatro de las resoluciones de las Naciones Unidas. Esto equivale a conservar la vegetación natural y seminatural en al menos el 50% de la superficie terrestre total de la Tierra (sin contar a la Antártida). Los esfuerzos de retención podrían contribuir a alcanzar múltiples objetivos simultáneamente, especialmente en donde la vegetación natural y seminatural puede gestionarse para lograr beneficios colaterales para la biodiversidad, el almacenamiento de carbono y la provisión de servicios ambientales. Esta gestión puede y debe ser impulsada y llevada a cabo por las personas que viven en y dependen de los lugares donde la vegetación natural y gestionada de forma sostenible permanece in situ y debe complementarse con la restauración y la gestión adecuada de entornos modificados por el hombre si se quieren alcanzar los objetivos globales.
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Conservación de los Recursos Naturales , Ecosistema , Humanos , Biodiversidad , Bosques , Regiones AntárticasRESUMEN
Precision medicine can significantly improve outcomes for patients with cancer, but implementation requires comprehensive characterization of tumor cells to identify therapeutically exploitable vulnerabilities. Here, we describe somatic biallelic TET2 mutations in an elderly patient with acute myeloid leukemia (AML) that was chemoresistant to anthracycline and cytarabine but acutely sensitive to 5'-azacitidine (5'-Aza) hypomethylating monotherapy, resulting in long-term morphological remission. Given the role of TET2 as a regulator of genomic methylation, we hypothesized that mutant TET2 allele dosage affects response to 5'-Aza. Using an isogenic cell model system and an orthotopic mouse xenograft, we demonstrate that biallelic TET2 mutations confer sensitivity to 5'-Aza compared with cells with monoallelic mutations. Our data argue in favor of using hypomethylating agents for chemoresistant disease or as first-line therapy in patients with biallelic TET2-mutated AML and demonstrate the importance of considering mutant allele dosage in the implementation of precision medicine for patients with cancer.
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Dioxigenasas , Leucemia Mieloide Aguda , Humanos , Ratones , Animales , Azacitidina , Leucemia Mieloide Aguda/genética , Estimación de Kaplan-Meier , Mutación , Proteínas de Unión al ADN/genética , Dioxigenasas/genéticaRESUMEN
Some patients with therapy-related myeloid neoplasms (t-MN) may have unsuspected inherited cancer predisposition syndrome (CPS). We propose a set of clinical criteria to identify t-MN patients with high risk of CPS (HR-CPS). Among 225 t-MN patients with an antecedent non-myeloid malignancy, our clinical criteria identified 52 (23%) HR-CPS patients. Germline whole-exome sequencing identified pathogenic or likely pathogenic variants in 10 of 27 HR-CPS patients compared to 0 of 9 low-risk CPS patients (37% vs. 0%, p = 0.04). These simple clinical criteria identify t-MN patients most likely to benefit from genetic testing for inherited CPS.
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Neoplasias Primarias Secundarias , Neoplasias , Humanos , Mutación de Línea Germinal , Neoplasias/genética , Mutación , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Neoplasias Primarias Secundarias/genéticaRESUMEN
Background@#Sleep is an essential occupation for students. It affects one's neurocognitive functions and psychomotor performance, playing a significant role in academic performance, health, and well-being. This study aims to describe the sleep quality and sleep patterns among undergraduate occupational therapy (OT) students at the University of Santo Tomas (UST) during the COVID-19 pandemic.@*Methods@#This descriptive cross-sectional study utilized a record review based on existing data from the UST OT Department's Student Life Survey 2021 database. A total of 205 students from different year levels and academic cohorts of the academic year 2021-2022 participated in the survey, which included the Pittsburgh Sleep Quality Index (PSQI). The data with valid responses (n=204) was analyzed using the measures of central tendency and dispersion, such as mean and standard deviation.@*Results@#Data analysis revealed that 95.59% (n=195) of student respondents had significantly poor sleep quality, while 4.41% (n=9) had good sleep quality. Students in the fifth-year level had the greatest sleep dysfunction as opposed to those in the third-year level who had little sleep dysfunction. Sleep duration and daytime dysfunction received the highest individual scores across all year levels.@*Conclusion@#Having poor sleep quality is a common occurrence among undergraduate OT students in UST during the COVID-19 pandemic. Sleep pattern trends suggest the need for school administrators and educators to create measures to mitigate possible negative effects on their student’s academic performance, health, and overall quality of life, especially during public health emergencies, calamities, and disasters.
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Calidad del Sueño , COVID-19RESUMEN
Secondary organic matter (SOM) formed from gaseous precursors constitutes a major mass fraction of fine particulate matter. However, there is only limited evidence on its toxicological impact. In this study, air-liquid interface cultures of human bronchial epithelia were exposed to different series of fresh and aged soot particles generated by a miniCAST burner combined with a micro smog chamber (MSC). Soot cores with geometric mean mobility diameters of 30 and 90 nm were coated with increasing amounts of SOM, generated from the photo-oxidation of mesitylene and ozonolysis of α-pinene. At 24 h after exposure, the release of lactate dehydrogenase (LDH), indicating cell membrane damage, was measured and proteome analysis, i.e. the release of 102 cytokines and chemokines to assess the inflammatory response, was performed. The data indicate that the presence of the SOM coating and its bioavailability play an important role in cytotoxicity. In particular, LDH release increased with increasing SOM mass/total particle mass ratio, but only when SOM had condensed on the outer surface of the soot cores. Proteome analysis provided further evidence for substantial interference of coated particles with essential properties of the respiratory epithelium as a barrier as well as affecting cell remodeling and inflammatory activity.
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Contaminantes Atmosféricos , Hollín , Humanos , Anciano , Contaminantes Atmosféricos/toxicidad , Proteoma , Material Particulado/toxicidad , Mucosa Respiratoria , Tamaño de la PartículaRESUMEN
Inflammatory responses are important in cancer, particularly in the context of monocyte-rich aggressive myeloid neoplasm. We developed a label-free cellular phenotypic drug discovery assay to identify anti-inflammatory drugs in human monocytes derived from acute myeloid leukemia (AML), by tracking several features ionizing from only 2500 cells using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry. A proof-of-concept screen showed that the BCR-ABL inhibitor nilotinib, but not the structurally similar imatinib, blocks inflammatory responses. In order to identify the cellular (off-)targets of nilotinib, we performed thermal proteome profiling (TPP). Unlike imatinib, nilotinib and other later-generation BCR-ABL inhibitors bind to p38α and inhibit the p38α-MK2/3 signaling axis, which suppressed pro-inflammatory cytokine expression, cell adhesion, and innate immunity markers in activated monocytes derived from AML. Thus, our study provides a tool for the discovery of new anti-inflammatory drugs, which could contribute to the treatment of inflammation in myeloid neoplasms and other diseases.
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Leucemia Mielógena Crónica BCR-ABL Positiva , Leucemia Mieloide Aguda , Citocinas , Resistencia a Antineoplásicos , Proteínas de Fusión bcr-abl/metabolismo , Humanos , Mesilato de Imatinib , Inflamación/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mieloide Aguda/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteoma , Pirimidinas , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
Leukemia cells re-program their microenvironment to augment blast proliferation and enhance treatment resistance. Means of clinically targeting such niche-driven treatment resistance remain ambiguous. We develop human induced pluripotent stem cell (hiPSC)-engineered niches to reveal druggable cancer-niche dependencies. We reveal that mesenchymal (iMSC) and vascular niche-like (iANG) hiPSC-derived cells support ex vivo proliferation of patient-derived leukemia cells, affect dormancy, and mediate treatment resistance. iMSCs protect dormant and cycling blasts against dexamethasone, while iANGs protect only dormant blasts. Leukemia proliferation and protection from dexamethasone-induced apoptosis is dependent on cancer-niche interactions mediated by CDH2. Consequently, we test CDH2 antagonist ADH-1 (previously in Phase I/II trials for solid tumors) in a very aggressive patient-derived xenograft leukemia mouse model. ADH-1 shows high in vivo efficacy; ADH-1/dexamethasone combination is superior to dexamethasone alone, with no ADH-1-conferred additional toxicity. These findings provide a proof-of-concept starting point to develop improved, potentially safer therapeutics targeting niche-mediated cancer dependencies in blood cancers.
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Células Madre Pluripotentes Inducidas , Leucemia , Neoplasias , Animales , Médula Ósea/patología , Dexametasona/farmacología , Resistencia a Antineoplásicos , Humanos , Leucemia/patología , Ratones , Neoplasias/patología , Microambiente TumoralRESUMEN
Global mean lower stratosphere temperatures rose abruptly in January 2020 reaching values not experienced since the early 1990s. Anomalously high lower stratospheric temperatures were recorded for 4 months at highly statistically significant levels. Here, we use a combination of satellite and surface-based remote sensing observations to derive a time-series of stratospheric biomass burning aerosol optical depths originating from intense SouthEastern Australian wildfires and use these aerosol optical depths in a state-of-the-art climate model. We show that the S.E. Australian wildfires are the cause of this lower stratospheric warming. We also investigate the radiatively-driven dynamical response to the observed stratospheric ozone perturbation and find a significant strengthening of the springtime Antarctic polar vortex suggesting that biomass burning aerosols play a significant role in the observed anomalous longevity of the ozone hole in 2020.
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Pérdida de Ozono , Ozono , Incendios Forestales , Aerosoles , Regiones Antárticas , Atmósfera/análisis , Australia , Ozono/análisisRESUMEN
Allograft failure remains a major barrier in the field of lung transplantation and results primarily from acute and chronic rejection. To date, standard-of-care immunosuppressive regimens have proven unsuccessful in achieving acceptable long-term graft and patient survival. Recent insights into the unique immunologic properties of lung allografts provide an opportunity to develop more effective immunosuppressive strategies. Here we describe advances in our understanding of the mechanisms driving lung allograft rejection and highlight recent progress in the development of novel, lung-specific strategies aimed at promoting long-term allograft survival, including tolerance.
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Rechazo de Injerto , Trasplante de Pulmón , Humanos , Tolerancia Inmunológica , Inmunosupresores , Trasplante HomólogoRESUMEN
Oxidation of isoprene by nitrate radicals (NO3) or by hydroxyl radicals (OH) under high NOx conditions forms a substantial amount of organonitrates (ONs). ONs impact NOx concentrations and consequently ozone formation while also contributing to secondary organic aerosol. Here we show that the ONs with the chemical formula C4H7NO5 are a significant fraction of isoprene-derived ONs, based on chamber experiments and ambient measurements from different sites around the globe. From chamber experiments we found that C4H7NO5 isomers contribute 5%-17% of all measured ONs formed during nighttime and constitute more than 40% of the measured ONs after further daytime oxidation. In ambient measurements C4H7NO5 isomers usually dominate both nighttime and daytime, implying a long residence time compared to C5 ONs which are removed more rapidly. We propose potential nighttime sources and secondary formation pathways, and test them using a box model with an updated isoprene oxidation scheme.
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Ambitious conservation efforts are needed to stop the global biodiversity crisis. In this study, we estimate the minimum land area to secure important biodiversity areas, ecologically intact areas, and optimal locations for representation of species ranges and ecoregions. We discover that at least 64 million square kilometers (44% of terrestrial area) would require conservation attention (ranging from protected areas to land-use policies) to meet this goal. More than 1.8 billion people live on these lands, so responses that promote autonomy, self-determination, equity, and sustainable management for safeguarding biodiversity are essential. Spatially explicit land-use scenarios suggest that 1.3 million square kilometers of this land is at risk of being converted for intensive human land uses by 2030, which requires immediate attention. However, a sevenfold difference exists between the amount of habitat converted in optimistic and pessimistic land-use scenarios, highlighting an opportunity to avert this crisis. Appropriate targets in the Post-2020 Global Biodiversity Framework to encourage conservation of the identified land would contribute substantially to safeguarding biodiversity.
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Biodiversidad , Conservación de los Recursos Naturales , HumanosRESUMEN
Organic aerosol (OA) is a key component of total submicron particulate matter (PM1), and comprehensive knowledge of OA sources across Europe is crucial to mitigate PM1 levels. Europe has a well-established air quality research infrastructure from which yearlong datasets using 21 aerosol chemical speciation monitors (ACSMs) and 1 aerosol mass spectrometer (AMS) were gathered during 2013-2019. It includes 9 non-urban and 13 urban sites. This study developed a state-of-the-art source apportionment protocol to analyse long-term OA mass spectrum data by applying the most advanced source apportionment strategies (i.e., rolling PMF, ME-2, and bootstrap). This harmonised protocol was followed strictly for all 22 datasets, making the source apportionment results more comparable. In addition, it enables quantification of the most common OA components such as hydrocarbon-like OA (HOA), biomass burning OA (BBOA), cooking-like OA (COA), more oxidised-oxygenated OA (MO-OOA), and less oxidised-oxygenated OA (LO-OOA). Other components such as coal combustion OA (CCOA), solid fuel OA (SFOA: mainly mixture of coal and peat combustion), cigarette smoke OA (CSOA), sea salt (mostly inorganic but part of the OA mass spectrum), coffee OA, and ship industry OA could also be separated at a few specific sites. Oxygenated OA (OOA) components make up most of the submicron OA mass (average = 71.1%, range from 43.7 to 100%). Solid fuel combustion-related OA components (i.e., BBOA, CCOA, and SFOA) are still considerable with in total 16.0% yearly contribution to the OA, yet mainly during winter months (21.4%). Overall, this comprehensive protocol works effectively across all sites governed by different sources and generates robust and consistent source apportionment results. Our work presents a comprehensive overview of OA sources in Europe with a unique combination of high time resolution (30-240 min) and long-term data coverage (9-36 months), providing essential information to improve/validate air quality, health impact, and climate models.
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Testimonio de Experto , Trasplante de Órganos , Animales , Selección de Paciente , Porcinos , Trasplante HeterólogoRESUMEN
Multiple languages being spoken within a species' distribution can impede communication among conservation stakeholders, the compilation of scientific information, and the development of effective conservation actions. Here, we investigate the number of official languages spoken within the distributions of 10,863 bird species to identify which species might be particularly affected by consequences of language barriers. We show that 1587 species have 10 languages or more spoken within their distributions. Threatened and migratory species have significantly more languages spoken within their distributions, when controlling for range size. Particularly high numbers of species with many languages within their distribution are found in Eastern Europe, Russia and central and western Asia. Global conservation efforts would benefit from implementing guidelines to overcome language barriers, especially in regions with high species and language diversity.
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Aves , Barreras de Comunicación , Animales , Comunicación , Conservación de los Recursos Naturales , Lenguaje , Federación de RusiaRESUMEN
BACKGROUND: Esophageal perforation is a morbid condition and remains a therapeutic challenge. We report the outcomes of a large institutional experience with esophageal perforation and identify risk factors for morbidity and mortality. METHODS: A retrospective analysis was conducted on 142 patients who presented with a thoracic or gastroesophageal junction esophageal perforation from 1995 to 2020. Baseline characteristics, operative or interventional strategies, and outcomes were analyzed by etiology of the perforation and management approach. Multivariable cox and logistic regression models were constructed to identify predictors of mortality and morbidity. RESULTS: Overall, 109 (77%) patients underwent operative intervention, including 80 primary reinforced repairs and 21 esophagectomies and 33 (23%) underwent esophageal stenting. Stenting was more common in iatrogenic (27%) and malignant (64%) perforations. Patients who presented with a postemetic or iatrogenic perforation had similar 90-day mortality (16% and 16%) and composite morbidity (51% and 45%), whereas patients who presented with a malignant perforation had a 45% 90-day mortality and 45% composite morbidity. Risk factors for mortality included age >65 years (hazard ratio [HR] 1.89 [1.02-3.26], P = 0.044) and a malignant perforation (HR 4.80 [1.31-17.48], P = 0.017). Risk factors for composite morbidity included pleural contamination (odds ratio [OR] 2.06 [1.39-4.43], P = 0.046) and sepsis (OR 3.26 [1.44-7.36], P = 0.005). Of the 33 patients who underwent stent placement, 67% were successfully managed with stenting alone and 30% required stent repositioning. CONCLUSIONS: Risk factors for morbidity and mortality after esophageal perforation include advanced age, pleural contamination, septic physiology, and malignant perforation. Primary reinforced repair remains a reasonable strategy for patients with an esophageal perforation from a benign etiology.